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The microbiological diagnosis of pleural effusion is largely based on classical microbiology methods, but these methods have a high rate of false negative results. Some previous studies have shown improved diagnostic performance for pathogens such as S. pneumoniae using molecular biology methods. We present the use of a Multiplex-PCR platform (BIOFIRE® FILMARRAY® Pneumonia Panel) for the etiological diagnosis of pleural effusion in pediatric pneumonia. We present a case series of 17 pleural fluid samples that were processed by culture-based microbiology and molecular biology methods. We document an increase in pathogen detection compared to culture-based methods. Additionally, the detection of viral pathogens in the pleural effusion was found, which are an important cause of pneumonia in pediatrics.